The primary cause of acquired immunodeficiency syndrome (AIDS) is the human immunodeficiency virus (HIV; See, e.g., Levy, 1993, Microbial. Rev. 57:183-289). There are two major HIV groups (HIV-1 and HIV-2) and many subgroups because the HIV genome mutates constantly. The major difference between the groups and subgroups is in the viral envelope. HIV-1 is classified into main subgroup (M) and a 10th outlier subgroup (O), in which subgroup M is divided into nine subtypes (clades) designed A through J (Hu et al., 1996, JAMA 275:210-216 and Korber et al., 1998, Science 280:1868-1871). The genetic variation seen in the HIV genome is the result of mutation, recombination, insertion, and deletion (Korber et al., 1998, Science 280:1868-1871). Still further genetic variation has come about as a result of human efforts including the construction of manmade recombinant simian-human immunodeficiency viruses (SHIVs), HIV DNA shuffling, and the inadvertent selection of drug-resistant HIV-1 strains through the use of monotherapy regimens or cocktail therapy. In particular, the mismatch polymerization of HIV reverse transcriptase (RT; van Der Hoek et al., 1998, J. Gen. Virol. 79:259-267) coupled with the high HIV production rate (more than 1010 virions per day; Perelson et al., 1996, Science 271:1582-1586), has facilitated the rapid generation of sequence variants. These processes in turn result in an extraordinary degree of antigenic variability, which permits subsequent immune evasion.
To date, no HIV vaccine has been shown to protect vaccinated individuals against HIV-1 infection (Mooij and Heeney, 2001, Vaccine, Vol.20:304-21). This is the case even though numerous vaccine modalities including inactivated viral, attenuated live, subunit, peptide, DNA, virus-like particle, pseudovirion, and live recombinant vector (e.g., BCG, vaccinia virus, polio virus, adenovirus, Salmonella, etc.) vaccines have been actively explored. Thus, there remains an urgent need in the art for the development of effective methods and compositions for combating immunodeficiency virus infections.